Mind-BodyMedicineforMultipleSclerosis:...

Hindawi Publishing CorporationAutoimmune DiseasesVolume 2012, Article ID 567324, 12 pagesdoi:10.1155/2012/567324

Review Article

Mind-Body Medicine for Multiple Sclerosis:A Systematic Review

Angela Senders,1 Helane Wahbeh,1 Rebecca Spain,1, 2 and Lynne Shinto1

1 Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA2 Department of Neurology, Portland Veterans Affairs Medical Center, Portland, OR 97239, USA

Correspondence should be addressed to Angela Senders, [email protected]

Received 8 August 2012; Accepted 6 October 2012

Academic Editor: D. N. Bourdette

Copyright © 2012 Angela Senders et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background. Mind-body therapies are used to manage physical and psychological symptoms in many chronic health conditions.Objective. To assess the published evidence for using mind-body techniques for symptom management of multiple sclerosis.Methods. MEDLINE, PsycINFO, and Cochrane Clinical Trials Register were searched from inception to March 24, 2012. Elevenmind-body studies were reviewed (meditation, yoga, biofeedback, hypnosis, relaxation, and imagery). Results. Four high qualitytrials (yoga, mindfulness, relaxation, and biofeedback) were found helpful for a variety of MS symptoms. Conclusions. The evidencefor mind-body medicine in MS is limited, yet mind-body therapies are relatively safe and may provide a nonpharmacologicalbenefit for MS symptoms.

1. Introduction

Multiple sclerosis (MS) is a chronic neurological disor-der with emotional, cognitive, and physical consequences.Patients can experience a diverse array of symptoms includ-ing impaired mobility, sensory disturbance, chronic pain,fatigue, bladder and bowel dysfunction, depression, andcognitive impairment. Patients report high levels of stress,independent of physical disability [1–3], and the risk ofdeveloping stress-related disorders like anxiety and depres-sion is high (25% and 34–50% lifetime prevalence, resp.) [4–7]. There is no cure for MS, and both disease-modifying andsymptomatic therapies have limitations in compliance due toside effects and cost [8, 9].

Mind-body therapies are used by a growing numberof American adults and children [10]. In a survey of1,110 MS patients, 32% of respondents had used mind-body modalities and reported a high perceived benefit [11].The National Center for Complementary and AlternativeMedicine defines mind-body therapies as those that integratethe brain, mind, body, and behavior, with the intent touse the mind to affect physical functioning and promotehealth [12]. Examples of such modalities include meditation,yoga, relaxation techniques, breathwork, visual imagery,

hypnotherapy, and biofeedback. While these practices varyin technique and application, they share a common objectiveto enhance the capacity of the mind to improve physical andpsychological wellbeing.

Many mind-body therapies can be taught in a clinicalsetting and then subsequently used at home by the patientin a self-directed way, making them ideal tools to promoteincreased self-efficacy. Mind-body techniques often have acalming effect on the autonomic nervous system [13] andthus may be helpful for conditions where psychological stressis a factor. From this perspective, mind-body interventionshold strong potential for use in MS. Broad reviews haveaddressed the use of mind-body therapies in general practice[14] and neurology [15], yet no comprehensive review ofevidence for MS exists. The objective of this paper is tosystematically review the published evidence for mind-bodytherapies for symptom management in MS.

2. Methods

One reviewer performed the searches, assessed inclusioncriteria, and extracted data on trial design and outcomes.Two reviewers independently assessed methodology and risk

2 Autoimmune Diseases

of bias for each study included in this paper. Because weexpected the sample size of mind-body studies to be small,we intentionally kept inclusion criteria broad.

2.1. Types of Studies. We included only controlled trials inthis paper.

2.2. Types of Participants. We included studies of any kindof MS. Studies that did not verify diagnosis of MS or useaccepted diagnostic criteria for their time were included inthis paper; however, their risk of bias is included in ouranalysis. We added the category “MS diagnosis confirmationand criteria” to the Cochrane Risk of Bias Table for thispurpose.

2.3. Types of Interventions. Mind-body therapies includedmeditation and mindfulness, yoga, hypnosis, biofeedback,relaxation, imagery, tai chi, and qi gong.

2.4. Types of Outcome Measures. Included were studieswith any MS outcome related to physical or psychosocialwellbeing. Specific outcomes were not defined.

2.5. Search Strategy for Identification of Studies. One reviewer(A. Senders) searched the electronic databases MEDLINE,PsychInfo, and Cochrane Clinical Trials Register. Databaseswere searched in Ovid (http://www.ovid.com/) from incep-tion to March 24, 2012, using the exploded medical subjectheadings (MeSH): Mind-Body Therapies; Mind-Body Rela-tions, Metaphysical; Therapeutics; Hypnosis; Yoga; Imagery;Biofeedback; Tai Ji; Meditation; Relaxation; Muscle Relax-ation; Relaxation Therapy; Breathwork; Breathing Exercises.Tai chi, Qi Gong, Breathing Technique, and Mindfulnesswere searched as keywords. These MeSH terms and keywordswere then combined with MS terms Multiple Sclerosis;Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis,Relapsing-Remitting. A medical librarian was consulted toreview the search protocol. Only studies reported in theEnglish language were considered in this review. A manualreview of references or related reviews was not completed.The specific search strategy can be found in the Appendix.

2.6. Selection of Studies. One author (A. Senders) conductedthe initial search. Potential publications were selected byscreening titles and abstracts for clinical trials that used amind-body intervention for any type of multiple sclerosis.Final selections were made by screening full articles for thefollowing inclusion criteria: any type of MS, any mind-body intervention, any kind of comparator group, and anyoutcome related to physical or mental wellbeing.

2.7. Data Extraction and Management. Data extraction fromeach study was performed by one author (A. Senders) usinga data collection form that included study design, participantcharacteristics, type and duration of intervention, compara-tor treatment, primary and secondary outcome measures,whether or not homework was prescribed, adherence to

homework, dropout rate/loss to follow up, and summary ofresults. Authors of reviewed studies were not contacted formissing information or clarification.

2.8. Assessment of Risk of Bias in Included Studies. Themethodological quality of clinical trials was assessed accord-ing to the Cochrane Risk of Bias Tool [36]. Assessmentsof bias were independently performed for each paper induplicate (AS, HW, or LS) and any disagreements wererecorded and resolved through discussion.

2.9. Issues of Heterogeneity. One objective of this paper wasto grade the body of evidence for mind-body medicine inMS using the Grading of Recommendations Assessment,Development and Evaluation tool (GRADE) [37]. However,a meta-analysis or reliable grading of the body of evidence isnot feasible due to a large amount of clinical and method-ological variability between studies. Instead we describe andreport on the state of the published evidence to date.

3. Results

Mind-body therapies are briefly described in Table 1. Whilethe therapies are described in discrete categories, consid-erable crossover exists between them. For example, guidedimagery is often included as a part of meditation andrelaxation protocols, yoga has a meditative component to it,and biofeedback for stress reduction often involves relaxationor autogenic training.

3.1. Search Results. Searching three electronic databasesrevealed a total of 106 articles. Titles and available abstractswere screened for clinical trials that used a mind-bodyintervention for MS; 87 articles were excluded because theywere nonintervention papers and 19 articles were identifiedfor further review (see Figure 1). From this, 10 studies wereselected based on the inclusion criteria above. Six mind-body modalities are included in this paper: two studies ofhypnosis, one of yoga, two of relaxation, two of mindfulness,two of biofeedback, and one study of guided imagery. Ofthe two mindfulness studies, one incorporated the principleof “mindfulness of movement” from tai chi/qi gong. Wecategorized this study as a mindfulness trial. No specificstudies of tai chi or qi gong were identified.

3.2. Description of Included Studies. A summary of thecharacteristics of the 10 studies is provided in Table 2.There were seven randomized controlled trials (RCTs)[25, 27, 30–34], one controlled trial in which the firsteight eligible subjects were enrolled in the experimentalgroup and the subsequent 14 subjects were randomized[28], one prospective cohort study with matched controls[26], and one prospective repeated measures design thatcompared within subject change between four differenthypnosis interventions [29]. Subjects were recruited fromlocal MS Society chapters, outpatient neurology clinics,community advertisements, rehabilitation centers, and localpractitioners. Sample sizes varied from 20 to 150; mean

Autoimmune Diseases 3

Table 1: Description of mind-body therapies and percent use by the general public.

Modality DescriptionUse by the

general public(%) [10]

Meditation

(i) A mental training that is a state of being more than a task. Practices incorporate self-observation andawareness, emotional and attentional regulatory strategies, and the cultivation of an attitude of acceptance.(ii) Many forms exist, share some distinctive features but vary in purpose and technique.(iii) Most widely researched forms include transcendental meditation and mindfulness meditation.

(a) Transcendental meditation: a silent word or phrase (a mantra) is repeated in order to reduce mentalactivity.(b) Mindfulness meditation: practitioners cultivate an open, nonjudgmental awareness of both internalexperiences (thoughts, emotions, and bodily sensations) and external experiences (sights, sounds) inthe present moment. Has been formalized for clinical intervention with mindfulness-based stressreduction, a program that is an amalgam of several mind-body techniques, including mindfulnessmeditation, breathing exercises, yoga postures, and relaxation techniques.

9.4

Yoga

(i) Incorporates physical postures, breathing, meditation into a multifaceted approach to physical/mentalwellbeing.(ii) Many different practices of yoga, each varying in focus.

(a) Hatha yoga is typically gentle with an emphasis on poses and breathwork.(b) Ashtanga and Vinyasa yoga are more physically demanding, moving from posture to posturewithout stopping.(c) Iyengar yoga is most concerned with precision of poses, encourages prop use to attain correctalignment.(d) Bikram Yoga is practiced in a heated room (typically 105◦F).(e) Kundalini yoga incorporates an added emphasis on the breath in conjunction with physical poses.

(iii) Like meditation, the practice of yoga cultivates a way of being rather than performing a task, although,Western practices that focus on exercise and physical health rather than awareness, insight, or spiritualityhave emerged.

6.1

Hypnosis

(i) Relaxed state of focused, inward attention in which peripheral awareness is reduced.(ii) Attaining alteration of consciousness involves absorption, dissociation, and suggestibility.

(a) Absorption: deep immersion in an internal experience.(b) Dissociation: disconnect from peripheral events that would normally be conscious (perceptions,thoughts, emotions, or sensory activity).(c) Suggestibility: suspension of conscious editing (not asking “why?”), respond to suggestion morereadily.

(iii) Therapist may use guided imagery or hypnotic suggestion to help the person to understand behavioralpatterns and envision making desired change.(iv) Self-hypnosis techniques can be used at home, reducing the cost of therapy and encouragingself-efficacy.

0.2

Biofeedback

(i) Electrodes placed on the body provide feedback to the patient about peripheral physiological markerslike heart rate, breathing rate, muscle tension, or electrodermal activity.(ii) Neurofeedback uses scalp electrodes to measure EEG activity.(iii) Information relayed with visual or auditory cues; patient can attempt to change thoughts, emotions, orbehaviors in order to control physiological reactions, such as slowing the heart rate or relaxing certainmuscles.(iv) Strategies are developed and refined with a practitioner, then utilized in real time outside thetherapeutic encounter.(v) Portable biofeedback devices available to enhance relaxation.(vi) Individualized treatment goals depend on the specific condition being addressed.

0.2

Relaxation

(i) Reduces reactivity to physical, psychosocial, and environmental stressors by reducing sympatheticnervous system arousal and enhancing parasympathetic response [16].(ii) The physiological counterpart of the fight-or-flight, response [17].(iii) Jacobson’s progressive muscular relaxation technique and autogenic training are formalized relaxationtechniques, all the mind-body therapies initiate some kind of relaxation response.(iv) Often incorporates breathing techniques that create awareness of breathing rate, rhythm, and volume.(v) Voluntary control of breathing patterns influences autonomic nervous system functions: heart ratevariability, cardiac vagal tone, and CNS excitation as indicated by EEG and MRI [18].(vi) Relaxation training enhances awareness of nervous system activation; patients can employ techniquesat any time to reduce reactivity.

15.6


Table 1: Continued.

Modality DescriptionUse by the

general public(%) [10]

Imagery

(i) Most prominent forms are guided imagery and motor imagery.(a) Guided imagery: involves visualization and imagination, goal of evoking a state of relaxation ora specific outcome (visualizing the repair of myelin, or one’s white blood cells attacking a tumor).(b) Motor imagery: patient relives the sensations of undertaking a skilled movement without actuallydoing the movement [19]. Physiologic similarities between physically executed and imaginedmovements have been noted in motor evoked potentials, MRI, PET, and EMG studies [20–24].

(ii) Can engage visual, tactile, kinesthetic, olfactory, gustatory, or any combination of these senses.(iii) Imagery typically developed and refined with a therapist, then practiced regularly outside thetherapeutic encounter. Motor imagery is used in addition to physical therapy or exercise and not as anisolated treatment.(iv) Tailored to condition and abilities, it should be practiced in patient’s own context to be meaningful fortheir progress.

2.2

Titles and abstracts identified from electronic databases and screened for retrieval: 106

Potentially appropriate full publications retrieved for full evaluation: 19

Excluded: 87

Total number of controlled trials included in review: 10

Excluded: 9 4 studies were not controlled 1 study had a comparator group but did not make between group comparisons1 study had outcomes that did not meet inclusion criteria 1 study purported relaxation training but in actualityprovided more neuropsych training than relaxation

1 study was a dissertation thesis

1 study had only one MS subject in an n of 30

Figure 1: Flow diagram of literature search and study selection process.

sample size was 46.6 ± 40.1. In total, 466 people withMS were studied. Only three of the studies reported MStype [25, 26, 30]. Two studies used McDonald criteria [38]to confirm diagnosis [25, 27], three reported diagnosisconfirmation by a neurologist but did not discuss criteria[26, 31, 32], two studies reported confirmed diagnoses butdid not report by who or how [30, 33], and three studiesdid not report whether MS diagnosis was confirmed or not[28, 29, 34]. Five studies measured participants’ baselineExpanded Disability Status Scale (EDSS) scores [25, 27, 30–32]; three of these studies provided mean EDSS scores forintervention and comparator groups. The EDSS is a measureof neurological impairment from 0 (normal neurologicalexam) to 10.0 (dead). Patients with scores in the 1.0–3.5range have mild disability with no limitation of walking,4.0–6.5 have increasing difficulty walking, and those 7.0 orhigher require a wheelchair [39]. The average baseline EDSSfor these five studies ranged from 2.9 to 5.9. The duration of

interventions varied from four weeks (one training session aweek) to 6 months (one training session a week). Assessmenttools varied greatly and included a range of subjective andobjective measures consisting of physical (disability, painintensity, fatigue, incontinence, and symptom checklists),psychological (mood profiles, anxiety, pain catastrophizing,and sense of control over health), cognitive (attention, mem-ory, and executive function), and quality of life measures.Eight studies specifically acknowledged asking participantsto practice techniques on their own as homework [25, 27–30, 32–34], and six of these studies made some attemptto quantify homework adherence [25, 27, 28, 30, 32, 33].Dropout rates and loss to follow-up ranged from 0% to 33%.

3.3. Methodological Quality of Included Studies. Table 3 sum-marizes the risk of bias for each study. Review authors’judgments are categorized as High risk of bias (−), Unclearrisk of bias (?), or Low risk of bias (+). Assessments


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ecti

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rin

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ence

and

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ptom

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ry),

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ric

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city

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me,

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ifica

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ble

2:C

onti

nu

ed.

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dyD

esig

nIn

terv

enti

onve

rsu

sco

mpa

riso

n

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ant

char

acte

rist

ics

Du

rati

onof

inte

rven

tion

Dro

pou

t/lo

ssto

follo

wu

pO

utc

omes

Res

ult

sO

vera

llri

skof

bias

Gh

afar

iet

al.,

2009

[32]

Con

trol

led

tria

l

PM

RTr

ain

ing

(n=

35)

vers

us

usu

alca

re(n=

35)

MS

type

not

spec

ified

16da

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trai

nin

gin

PM

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rim

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ity

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F-8)

.

PM

Rtr

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ing

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psh

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ifica

nt

impr

ovem

ents

inqu

alit

yof

life

com

pare

dto

usu

alca

reco

ntr

ols

(P<.0

04).

Low

Suth

erla

nd

etal

.,20

05[3

3]R

CT

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toge

nic

trai

nin

g(n=

14)

vers

us

usu

alca

re(n=

12)

MS

type

not

spec

ified

1se

ssio

n/w

k×

10w

ks15

%

Qu

alit

yof

life

(MSQ

OL

),m

ood

(PO

MS-

SF),

depr

essi

on(C

ES-

D).

(No

prim

ary

outc

omes

stat

ed.)

AT

grou

pre

por

ted

mor

een

ergy

than

con

trol

grou

p(P=.0

1)an

dw

ere

less

limit

edin

thei

rro

les

due

toph

ysic

alan

dem

otio

nal

prob

lem

s(P=.0

2,P=.0

5).N

osi

gnifi

can

tdi

ffer

ence

sbe

twee

ngr

oups

wer

ese

enfo

rm

ood

orde

pres

sion

.

Un

clea

r

Mag

uir

e,19

96[3

4]R

CT

Imag

ery

(n=

15)

vers

us

usu

alca

re(n=

18)

MS

type

not

spec

ified

Six

1-h

our

grou

pse

ssio

ns

0%

Moo

d(P

OM

S),a

nxi

ety

(STA

I),

hea

lth

attr

ibu

tion

(HA

T),

MS

sym

ptom

chec

klis

t(d

evel

oped

byP

I).(

No

prim

ary

outc

omes

stat

ed.)

Imag

ery

grou

psh

owed

no

chan

gein

moo

dco

mpa

red

toco

ntr

ols.

Imag

ery

show

edde

crea

sein

stat

ean

xiet

yaf

ter

inte

rven

tion

(P<.0

5)bu

tn

ottr

ait

anxi

ety

com

pare

dto

con

trol

s.T

he

“in

tern

alco

ntr

olof

hea

lth”

scor

efo

rim

ager

ygr

oup

rem

ain

edst

able

but

decr

ease

dfo

rco

ntr

ols

(P<.0

5).

Un

clea

r

BP

I:B

rief

Pain

Inve

nto

ry;

CE

S-D

:C

ente

rfo

rE

pide

mio

logi

cSt

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es-D

epre

ssio

nSc

ale;

ESt

im:

Neu

rom

usc

ula

rel

ectr

ical

stim

ula

tion

;H

AQ

UA

MS:

Ham

burg

Qu

alit

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Qu

esti

onn

aire

inM

ult

iple

Scle

rosi

s;H

AT

:H

ealt

hA

ttri

buti

onTe

st;

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:In

con

tin

ence

Impa

ctQ

ues

tion

nai

re;

KH

Q:

Kin

g’s

Hea

lth

Qu

esti

onn

aire

;M

FI:

Mu

ltid

imen

sion

alFa

tigu

eIn

ven

tory

;M

FIS:

Mod

ified

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gue

Inve

nto

rySc

ale;

MSQ

OL

:M

SQ

ual

ity

ofLi

feIn

stru

men

t;N

RS:

Nu

mbe

rR

atin

gSc

ale;

PASA

T:P

aced

Au

dito

rySe

rial

Add

itio

nTe

st;P

CS:

Pain

Cat

astr

oph

izin

gSc

ale;

PFT

:pel

vic

floo

rtr

ain

ing;

PM

R:p

rogr

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usc

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tion

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Pro

file

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ood

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es-S

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rm;P

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ate

Trai

tA

nxi

ety

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nto

ry;U

DI:

Uri

nar

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∗ Tot

aln

um

ber

ofse

ssio

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over

wh

atle

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hof

tim

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un

clea

r.


Ta

ble

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dyIn

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Inco

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isan

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iter

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ther

bias∗

Ove

rall

risk

ofbi

asfo

rst

udy

Gro

ssm

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[25]

Min

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+−

++

++

?+

McC

lurg

etal

.,20

06[3

0]B

iofe

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++

++

++

Kla

rsko

vet

al.,

1994

[31]

Bio

feed

back

??

−−

++

?−

−Je

nse

net

al.,

2011

[29]

Hyp

nos

is?

?−

+−

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09[2

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ypn

osis

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?+

++

++

Suth

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nd

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05[3

3]R

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96[3

4]Im

ager

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+?

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(+)

Low

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( −)

Hig

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.(?

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∗ Oth

erbi

asca

tego

ryin

clu

des

smal

lsam

ple

size

(n<

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[35]

,stu

dies

wh

ich

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rted

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gu

nde

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ered

and

min

imal

orn

ogr

oup

com

pari

son

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selin

e.


Table 4: Of 10 studies reviewed, four high quality studies werefound helpful for symptoms of MS.

Study Intervention Helpful for

Ghafari et al.,2009 [32]

Relaxation Quality of Life

Grossman et al.,2010 [25]

Mindfulness-basedstress reduction

DepressionAnxietyFatigueQuality of Life

Oken et al.,2004 [27]

Yoga Fatigue

McClurg et al.,2006 [30]

Biofeedback Bladder incontinence

consider the risk of bias of sufficient magnitude to have anotable impact on the results or conclusions of the trial.Several of the studies failed to provide enough detail foradequate assessment. Details regarding random sequencegeneration and allocation concealment were particularlypoorly reported. Three studies did not provide sufficientdetails about baseline characteristics of comparison groups[28, 29, 31]. As it is impossible to blind participants tointerventions that require their active involvement, all 10studies received High risk of bias scores for this category.Sample sizes were generally small and seven of the studieshad ≤33 subjects. Only three studies provided intention totreat analysis [25, 27, 30]. Overall, we found four of the 10studies to be methodologically sound [25, 27, 30, 32], threeto have an Unclear risk of bias [28, 33, 34], and three to havehigh overall risk of bias (Table 3) [26, 29, 31].

4. Discussion

The objective of this paper was to assess the publishedevidence for using mind-body techniques for symptommanagement of multiple sclerosis. Four high quality studiesshowed that mindfulness, yoga, biofeedback, and relaxationhad a positive effect on depression, anxiety, fatigue, qualityof life, and bladder incontinence (Table 4) and no effect ondisability, executive function, or other cognitive measures.The remaining studies demonstrated benefit for balance anddaily pain intensity, but had no effect on executive function,mood, or disability—although many methodological inade-quacies were identified. This paper demonstrates that studiesof mind-body techniques for treating MS symptoms arefeasible, and that more stringently designed, well-executedresearch is needed in this population to determine efficacy.

4.1. Implications for Research. More rigorous research isneeded utilizing mind-body techniques for MS. Of the fewstudies identified in this paper, most were not of highquality, often due to small numbers and a lack of assessorblinding. In trials where it is impossible to blind participantsto the study intervention, it is imperative to ensure thatthose assessing outcomes have no knowledge of the subjects’group assignment. Reporting on the blinding methodology

for outcome assessors including maintenance of blindingthroughout the study will improve the quality of future trials.

Placebo effects due to expectation are important to assessin trials where subjects are not blinded. Because subjectsknow which intervention group they will be participatingin, it is possible that anticipation of improvement mayinfluence outcomes. Only one study in this paper evaluatedexpectation effects. Jensen et al., 2009 found that expectancywas associated with a positive treatment outcome in responseto self-hypnosis training for chronic pain. It is importantto measure such relationships so that expectancy effectsare distinguished from true intervention effects, and theimpact of expectancy on outcome can be determined. Fur-thermore, such research may help identify ways to enhanceexpectancy in the clinical setting. In clinical practice whenpatients are given a known therapy, the effectiveness of thetherapy is a combination of nonspecific and biologicallyactive effects. Understanding the nonspecific effects thatcontribute to beneficial findings in trials (e.g., expectation,self-efficacy, motivation for improvement, locus of control,patient/provider relations, and attitudes toward one’s diseaseand healing) will further our knowledge of mind-bodytherapies and enhance the generalizability of research trialsto clinical practice.

The selection of appropriate comparison groups iscritical when designing nonblinded intervention trials usingmind-body techniques. Six studies in this paper used anonintervention control group (either usual care or waitlist)[25–27, 32–34]. A limitation of this design is that it doesnot control for nonspecific factors involved in the treatmentgroup like social effects of group work and attention frominstructors [40]. A well-chosen active comparison group cancontrol both treatment-specific and nonspecific effects ofthe study intervention, although this kind of comparisonhas disadvantages as well. A drawback to active controls isthat they can exert their own therapeutic benefit beyondnonspecific social effects, thus making comparisons betweengroups difficult to interpret [41]. For example, Oken etal. compared yoga with an active control (exercise) toevaluate yoga-specific effects and control time and attentionof the intervention and found few differences betweengroups. Exercise is known to have a therapeutic benefit inMS [42] and this could have been problematic had theauthors not also included a nonintervention (waitlist) groupfor comparison. Three-arm trials that include both activeand nonintervention controls are favorable if they can beafforded. Challenges regarding control group selection formind-body medicine are not new and have been describedby others [41, 43, 44].

Level of disability should be considered during the designof a study. One example is highlighted by the Klarskov study[31]. The biofeedback protocol in this trial was specificallydesigned to enhance the awareness of muscles in the pelvicfloor, yet 11 of the 20 subjects could not voluntarily contractpelvic floor muscles as measured by EMG, and 18 of the20 subjects were unable to contract muscles voluntarily asmeasured by digital exam. The goal of the intervention wasto use EMG feedback and yet a majority of the participantswere unable to produce an EMG signal. Thus, the high


baseline disability scores may have accounted for the absenceof biofeedback effect between groups. Inclusion criteria fora baseline disability that allowed for an appropriate EMGfeedback would have strengthened the study design andhelped determine a therapeutic benefit.

While it may appear self-evident that mind-body ther-apies have a favorable risk-benefit ratio, only one studyspecifically discussed safety in terms of adverse events [27].Four papers reported why subjects dropped out of thestudy, but furnished no other safety information [25, 26, 30,33]. Based on limited data, no intervention-related safetyissues were identified in this paper. Even though mind-body interventions are typically gentle and serious adverseevents, unlikely, future trials should collect data necessary tocalculate appropriate risk assessments.

In order to advance mind-body research for MS, futurestudies must attempt to adequately power their trials for anappropriate sample size. Only three studies reported poweranalyses a priori and as a result had adequate sample sizes[25, 27, 32]. The remaining trials did not benefit from poweranalyses and thus risked type II error, or false negative results.

4.2. Implications for Practice. Mind-body therapies are valu-able because they can improve symptoms that affect qualityof life. For example, fatigue is one of the most common andtroubling symptoms in MS. MS-related fatigue is associatedwith decreased quality of life and depression and is describedas the worst symptom of MS by 69% of patients [45]. It isestimated that 75–95% of MS patients suffer from fatigue[45, 46] and pharmaceutical treatment provides limitedrelief. Our paper found that both yoga and mindfulnesstraining improved MS fatigue, offering support with fewerside effects than conventional treatment. Therapies that canimprove quality of life and the patient’s ongoing experienceof MS are essential to the successful management of thisdisease.

While there are not enough research studies to providestrong evidence for the use of mind-body therapies inMS, there is no evidence stating that they are harmfuleither. Patients who express interest in participating in suchtherapies do not necessarily need to be dissuaded because ofharmful effects. However, clinicians should be mindful of afew key points when discussing mind-body medicine withMS patients.

(i) Hypnosis can allow distressing, repressed psycholog-ical content to come into consciousness and maynot be appropriate for some patients with psychiatricdisorders [47].

(ii) Guided or motor imagery requires that individualsimagine themselves performing a task, including thesensations that may accompany that activity and maynot be suitable for patients with substantial cognitiveimpairment [48].

(iii) Yoga may not be appropriate for people withmusculoskeletal conditions unless postures can bemodified for individual circumstances. Props, suchas cushions, blocks, and straps, can aid patients in

holding poses, requiring less muscular effort. BikramYoga is practiced in a heated room (typically 105◦)and risks exacerbating MS symptoms [49]. Workingwith a teacher who has experience adapting yogapractice for those with disabilities is advised.

(iv) Practitioner training and licensing may be an issuefor some modalities. Health care providers can usebiofeedback devices within the scope of practicedefined by their license. Voluntary certification isavailable [50] for those who do not hold a health carelicense, but is not currently required by most states.Thus, training and experience may vary greatly fromone therapist to the next and should be investigated.Hypnosis is typically practiced as an adjunct to psy-chotherapy by mental health care providers; however,most states do not require a license to practice anda hypnotherapist’s credentials should be investigated.Patients should be advised to seek out appropriatelytrained providers for the modality they are interestedin.

4.3. Limitations of This Paper. The current study had limita-tions that should be considered in interpreting the results.A single author performed database searches, conductedinitial reviews, and extracted data; thus the initial studyselection and data extraction may have been subject to biasand error. To address this, a librarian formulated a secondsearch strategy that failed to retrieve any new articles (seethe Appendix). That both search strategies retrieved identicalresults suggests no bias at the initial searching level. OnlyEnglish language trials were included. Including foreignlanguage search results may have contributed additionalstudies. Other studies may have been inadvertently missedbecause a manual search of references and reviews wasnot done. Authors were also not contacted for missinginformation. Regardless of these limitations, this is thefirst paper to assess the published research for mind-bodymedicine in MS. This is a starting point upon which onecan build further assessment of the efficacy and feasibility ofmind-body therapies for MS.

5. Conclusion

We found evidence to suggest that mind-body therapiesare effective for treating common MS symptoms, includingfatigue, anxiety, depression, incontinence, and quality of life.Mind-body modalities appear safe, can be prescribed as anadjunct to conventional care, and may be especially helpfulwhen psychosocial stress is a factor or non-pharmacologicaloptions are desired (e.g., polypharmacy, pregnancy, andpatient preference). More rigorously designed trials of mind-body interventions applied specifically to MS are neededin order to determine their efficacy and optimal selectionfor specific MS symptoms. Such research will enhance ourunderstanding of the clinical effects of mind-body medicineas well as increase awareness and availability to clinicians andpatients alike.


Appendix

Two search strategies were applied to each electronic data-base: MEDLINE, PsycINFO, and Cochrane Clinical TrialsRegister.

(1) Hannon search strategy: (exp Mind-Body TherapiesOR exp Mind-Body Relations, Metaphysical) AND(exp therapeutics OR th.fs.) AND exp multiplesclerosis OR multiple sclerosis, chronic progressiveOR multiple sclerosis, relapsing-remitting).

(2) Senders search strategy: (exp multiple sclerosis ORmultiple sclerosis, chronic progressive OR multiplesclerosis, relapsing-remitting) AND (qi gong.mp.OR exp Meditation OR mindfulness.mp. OR expRelaxation OR exp Muscle Relaxation OR expRelaxation Therapy OR exp Breathing Exercises ORbreathing technique.mp. OR breathwork.mp. ORbreathwork.mp. OR exp Hypnosis OR exp “Imagery(Psychotherapy)” OR exp Yoga OR exp Biofeedback,Psychology OR exp Tai Ji OR tai chi.mp.).

Conflict of Interests

The authors have no conflict of interests.

Acknowledgments

The authors thank Marian McDonagh for valuable directionand Todd Hannon for help with the search strategies. Thiswork was supported by the Oregon Clinical and TranslationalResearch Institute Grant number UL1 RR024140 from theNational Center for Research Resources and the NationalCenter for Advancing Translational Sciences of the NationalInstitutes of Health, and the National Center for Comple-mentary and Alternative Medicine of the National Institutesof Health Grant numbers AT002688, K01AT004951. Thecontent of this paper is solely the responsibility of the authorsand does not necessarily represent the official views of theNational Institutes of Health.

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